Dentithecamides A-H, Diacylated Zoanthoxanthin Derivatives with PAX3-FOXO1 Inhibitory Activity from the Hydroid Dentitheca habereri .

Chemical investigation of the marine hydroid Dentitheca habereri led to the identification of eight new diacylated zoanthoxanthin alkaloids, named dentithecamides A-H ( 1 - 8 ), along with three previously reported analogues, zoamides B-D ( 9 - 11 ). The structures of compounds 1 - 11 were elucidated by spectroscopic and spectrometric analyses, including IR, HRESIMS, and NMR experiments, and by comparison with literature data. Compounds 1 - 11 are the first zoanthoxanthin alkaloids to be reported from a hydroid. Dentithecamides A ( 1 ) and B ( 2 ) along with zoamides B-D ( 9 - 11 ), which all share a conformationally mobile cycloheptadiene core, inhibited PAX3-FOXO1 regulated transcriptional activity and thus provided a structural framework for the potential development of more potent PAX3-FOXO1 inhibitors.